study focused on the immunological response to pentavalent toxoids. In the first part of the experiment, 17 laboratory workers received 0.5-ml injections of a pentavalent toxoid on a 0-, 2-, and 10-week schedule. As a control group, additional personnel received a univalent toxoid on the same schedule (each univalent toxoid [A, B, C, D, or E] was given to five or six individuals). Four months later an additional 15 individuals received the same lot of the pentavalent toxoid on the same schedule. Satisfactory antitoxin titer levels were seen in these initial experiments. Groups of 30 individuals (the study does not indicate the number of groups or whether the individuals were new participants) were then immunized with one of the pentavalent toxoid lots on a 0-, 2-, and 12-week schedule, with a booster at 52 weeks. The only statement about adverse reactions made by the investigators in their report was that 400 individuals received the pentavalent toxoid with “no marked local or marked systemic reactions.” Three persons had either a moderate local or moderate systemic reaction (the authors provided no details), and the authors stated that the incidence of mild local reaction was somewhat greater for the pentavalent toxoids than the control group toxoids (Fiock et al., 1962).

Other Studies and Reports

The committee received reports on several other studies, discussed below, with information on the botulinum toxoid vaccine. These studies have not been published in the peer-reviewed literature and were not considered in the committee’s conclusions regarding the strength of the evidence for associations between botulinum toxoid and adverse health outcomes.

USAMRIID studies. The Proceedings of the 1981 International Conference on the Biomedical Aspects of Botulism (Lewis, 1981) details further studies on the pentavalent toxoids. Investigators at USAMRIID hypothesized that injections with formulations of the pentavalent botulinum toxoid containing less formaldehyde preservative would result in reduced pain at the site of injection. They conducted a full-series double-blind study to evaluate two formulations of the pentavalent toxoid with varying formaldehyde content; 36 previously nonimmunized laboratory workers received injections at 0, 14, and 84 days (13 individuals received the low-formaldehyde lot, 11 received the higher-formaldehyde lot, and 12 received the control toxoid [with an intermediate level of formaldehyde]). Reactions were recorded immediately and then at 24, 48, and 72 hours in all volunteers and after 72 hours as needed. The study reported no discernible differences in immediate pain. The group receiving the low-formaldehyde lot reported a slightly higher percentage of moderate local reactions (17.9 percent compared to 15 percent in those receiving the high-formaldehyde lot and 3 percent of controls). Moderate reactions were defined as edema or induration >30 mm and < 210 mm in any one diameter. No severe reactions occurred for any of the lots.

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